Our previous studies indicate that surfactant protein (SP)-A, SP-B, and SP-C mRNA levels are decreased in lungs of fetuses of streptozotocin diabetic(STZ-DB) rats. The STZ-DB rat model is associated with fetal hyperglycemia, but with low to normal insulin levels. We have also shown that high glucose, but not insulin, results in significantly reduced incorporation of H3-choline into disaturated phosphatidylcholine in day 20 fetal lung explants. These results led us to hypothesize that increased glucose concentrations per se may be an important factor in inhibiting SP mRNA levels. We therefore studied the effect of increasing concentrations of glucose on surfactant protein (SP) gene expression in vitro.

Northern blot analysis of SP-A, SP-B, and SP-C mRNA was performed on fetal day-20 lung explants cultured for ≈48 hours in medium containing 10, 25, 50, and 100mM glucose. Quantitation of SP mRNA levels was performed using laser densitometry and was normalized using β-actin mRNA levels as a control. No consistent changes were noted in SP-A mRNA levels at different glucose concentrations. However, when compared to control (=10mM glucose), mRNA levels of the hydrophobic proteins SP-B and SP-C were reduced in a dose-dependent manner by increasing glucose concentrations: at 25mM glucose the mRNA levels were decreased to 50-60% of control, at 50mM glucose to 20-25% of control, and at 100mM glucose to <10% of control (p<.001).

These findings suggest that the decreases in SP-B and SP-C mRNA in STZ-DB rats are primarily the result of a direct effect of hyperglycemia, whereas the decrease in SP-A mRNA levels in STZ-DB rats appears to be due to other effects of diabetes in pregnancy.

(Supported by NIH RO1 HL-38288.)